DiNuP: a systematic approach to identify regions of differential nucleosome positioning

Motivation: With the rapid development of high-throughput sequencing technologies, the genome-wide profiling of nucleosome positioning has become increasingly affordable. Many future studies will investigate the dynamic behaviour of nucleosome positioning in cells that have different states or that are exposed to different conditions. However, a robust method to effectively identify the regions of differential nucleosome positioning (RDNPs) has not been previously available. Results:: We describe a novel computational approach, DiNuP, that compares nucleosome profiles generated by high-throughput sequencing under various conditions. DiNuP provides a statistical P-value for each identified RDNP based on the difference of read distributions. DiNuP also empirically estimates the false discovery rate as a cutoff when two samples have different sequencing depths and differentiate reliable RDNPs from the background noise. Evaluation of DiNuP showed it to be both sensitive and specific for the detection of changes in nucleosome location, occupancy and fuzziness. RDNPs that were identified using publicly available datasets revealed that nucleosome positioning dynamics are closely related to the epigenetic regulation of transcription. Availability and implementation: DiNuP is implemented in Python and is freely available at http://www.tongji.edu.cn/~zhanglab/DiNuP

The Diagonally Dominant Degree and Disc Separation for the Schur Complement of Ostrowski Matrix

By applying the properties of Schur complement and some inequality techniques, some new estimates of diagonally and doubly diagonally dominant degree of the Schur complement of Ostrowski matrix are obtained, which improve the main results of Liu and Zhang (2005) and Liu et al. (2012). As an application, we present new inclusion regions for eigenvalues of the Schur complement of Ostrowski matrix. In addition, a new upper bound for the infinity norm on the inverse of the Schur complement of Ostrowski matrix is given. Finally, we give numerical examples to illustrate the theory results

Effect of reservoir heterogeneity on CO2 flooding in tight oil reservoirs

Carbon dioxide (CO2)-enhanced oil recovery (EOR) has great potential and opportunity for further development, and it is one of the vital carbon capture, utilization, and storage (CCUS) technologies. However, strong heterogeneity is one of the several challenges in developing reservoirs, especially for China’s continental tight oil reserves. This study investigates the effects of heterogeneous porosity and permeability on CO2 flooding evolution in low-permeable tight formation. We simulated CO2-EOR using a numerical model developed on the platform of TOUGH2MP-TMVOC to evaluate the effect of different levels of heterogeneity on oil production, gas storage, and flow behaviors in a tight reservoir, controlled by standard deviation and correlation length. A comparison of nine cases reveals that porosity heterogeneity commonly intensifies flow channeling, and there is an oil production decline with higher standard deviation and longer correlation length of porosity field. In addition, the porosity correlation length has a negligible effect on reservoir performance when the standard deviation is relatively low. Furthermore, strong heterogeneity also has a negative impact on the storage capacity of CO2 and oil production. Notably, as the standard deviation was raised to 0.1, a small sweep region arose with the early CO2 breakthrough, which led to a worse flooding effect. Finally, this study exemplifies that a higher injection/production rate and CO2 alternating N2 injection strategies can improve oil recovery in highly heterogeneous reservoirs

A review of CO2 storage in view of safety and cost-effectiveness

The emissions of greenhouse gases, especially CO2, have been identified as the main contributor for global warming and climate change. Carbon capture and storage (CCS) is considered to be the most promising strategy to mitigate the anthropogenic CO2 emissions. This review aims to provide the latest developments of CO2 storage from the perspective of improving safety and economics. The mechanisms and strategies of CO2 storage, focusing on their characteristics and current status, are discussed firstly. In the second section, the strategies for assessing and ensuring the security of CO2 storage operations, including the risks assessment approach and monitoring technology associated with CO2 storage, are outlined. In addition, the engineering methods to accelerate CO2 dissolution and mineral carbonation for fixing the mobile CO2 are also compared within the second section. The third part focuses on the strategies for improving economics of CO2 storage operations, namely enhanced industrial production with CO2 storage to generate additional profit, and co-injection of CO2 with impurities to reduce the cost. Moreover, the role of multiple CCS technologies and their distribution on the mitigation of CO2 emissions in the future are summarized. This review demonstrates that CO2 storage in depleted oil and gas reservoirs could play an important role in reducing CO2 emission in the near future and CO2 storage in saline aquifers may make the biggest contribution due to its huge storage capacity. Comparing the various available strategies, CO2-enhanced oil recovery (CO2-EOR) operations are supposed to play the most important role for CO2 mitigation in the next few years, followed by CO2-enhanced gas recovery (CO2-EGR). The direct mineralization of flue gas by coal fly ash and the pH swing mineralization would be the most promising technology for the mineral sequestration of CO2. Furthermore, by accelerating the deployment of CCS projects on large scale, the government can also play its role in reducing the CO2 emissions

Local chromatin dynamics of transcription factors imply cell-lineage specific functions during cellular differentiation

Chromatin dynamics across cellular differentiation states is an emerging perspective from which the mechanism of global gene expression regulation may be better understood. While the roles of some histone marks have been partially interpreted in terms of their association with gene transcription, the dynamics of histone marks from a loci-specific perspective during cellular differentiation is not well studied. We established a method to systematically assess the histone modification variations of genes across various cellular differentiation states. We calculated the histone modification variation scores of H3K4me3, H3K27me3 and H3K36me3 for over 1300 curated transcription factors (TFs) during human blood cell differentiation. Hematopoietic-specific TFs (identified by literature mining) were significantly overrepresented by TFs with higher histone modification variation scores. Hierarchical clustering of all TFs based on the histone modification variation scores defined a group of TFs where known or potential hematopoietic-specific TFs were remarkably enriched. Our results suggest that local chromatin state dynamics of transcription factors across cellular differentiation states could imply cell lineage-specific functions. More importantly, our method can be applied to broader systems, holding the promise to discover de novo, lineage-specific TFs by interrogating their histone modification dynamics across cell lineages

Human-centered design and evaluation of AI-empowered clinical decision support systems: a systematic review

IntroductionArtificial intelligence (AI) technologies are increasingly applied to empower clinical decision support systems (CDSS), providing patient-specific recommendations to improve clinical work. Equally important to technical advancement is human, social, and contextual factors that impact the successful implementation and user adoption of AI-empowered CDSS (AI-CDSS). With the growing interest in human-centered design and evaluation of such tools, it is critical to synthesize the knowledge and experiences reported in prior work and shed light on future work.MethodsFollowing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a systematic review to gain an in-depth understanding of how AI-empowered CDSS was used, designed, and evaluated, and how clinician users perceived such systems. We performed literature search in five databases for articles published between the years 2011 and 2022. A total of 19874 articles were retrieved and screened, with 20 articles included for in-depth analysis.ResultsThe reviewed studies assessed different aspects of AI-CDSS, including effectiveness (e.g., improved patient evaluation and work efficiency), user needs (e.g., informational and technological needs), user experience (e.g., satisfaction, trust, usability, workload, and understandability), and other dimensions (e.g., the impact of AI-CDSS on workflow and patient-provider relationship). Despite the promising nature of AI-CDSS, our findings highlighted six major challenges of implementing such systems, including technical limitation, workflow misalignment, attitudinal barriers, informational barriers, usability issues, and environmental barriers. These sociotechnical challenges prevent the effective use of AI-based CDSS interventions in clinical settings.DiscussionOur study highlights the paucity of studies examining the user needs, perceptions, and experiences of AI-CDSS. Based on the findings, we discuss design implications and future research directions

Repulsive guidance molecule B inhibits metastasis and is associated with decreased mortality in non-small cell lung cancer

Repulsive guidance molecules (RGMs) are co-receptors of bone morphogenetic proteins (BMPs) and programmed death ligand 2 (PD-L2), and might be involved in lung and other cancers. We evaluated repulsive guidance molecule B (RGMB) expression in 165 non-small cell lung cancer (NSCLC) tumors and 22 normal lung tissue samples, and validated the results in an independent series of 131 samples. RGMB was downregulated in NSCLC (P ≤ 0.001), possibly through promoter hypermethylation. Reduced RGMB expression was observed in advanced-stage tumors (P = 0.017) and in tumors with vascular invasion (P < 0.01), and was significantly associated with poor overall survival (39 vs. 62 months, P < 0.001) and with disease-associated patient mortality (P = 0.015). RGMB knockdown promoted cell adhesion, invasion and migration, in both NSCLC cell lines and an in vivo mouse model, which enhanced metastatic potential. Conversely, RGMB overexpression and secretion suppressed cancer progression. The tumor-suppressing effect of RGMB was exerted through inhibition of the Smad1/5/8 pathway. Our results demonstrate that RGMB is an important inhibitor of NSCLC metastasis and that low RGMB expression is a novel predictor or a poor prognosis